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| Profile Name | BRAF G469A |
| Gene Variant Detail | |
| Relevant Treatment Approaches | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor |
| Molecular Profile | Indication/Tumor Type | Response Type | Relevant Treatment Approaches | Therapy Name | Approval Status | Evidence Type | Efficacy Evidence | References |
|---|---|---|---|---|---|---|---|---|
| BRAF G469A | lung non-small cell carcinoma | sensitive | TAE226 | Preclinical | Actionable | In a preclinical study, TAE226 treatment inhibited proliferation of non-small cell lung carcinoma cell lines harboring BRAF G469A mutation in culture (PMID: 26090892). | 26090892 | |
| BRAF G469A | Advanced Solid Tumor | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Zelboraf (vemurafenib) did not inhibit MEK and ERK activation in transformed cells over expressing the constitutively dimerized BRAF G469A (PMID: 26343582). | 26343582 | |
| BRAF G469A | lung non-small cell carcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, treatment with the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) resulted in decreased viability and enhanced ERK inhibition compared to either agent alone, in a non-small cell lung cancer cell line harboring BRAF G469A in culture (PMID: 28947956). | 28947956 |
| BRAF G469A | lung non-small cell carcinoma | resistant | Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, a non-small cell lung cancer cell line harboring BRAF G469A demonstrated resistance to induction of apoptosis by Zelboraf (vemurafenib,) and treatment with Zelboraf (vemurafenib) was not effective in inhibiting growth in culture (PMID: 25706985). | 25706985 | |
| BRAF G469A | lung non-small cell carcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, Mekinist (trametinib) induced apoptosis and inhibited growth of a non-small cell lung cancer cell line harboring BRAF G469A in culture (PMID: 25706985). | 25706985 |
| BRAF G469A | lung non-small cell carcinoma | conflicting | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib + Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, the combination of Mekinist (trametinib) and Zelboraf (vemurafenib) inhibited growth of a non-small cell lung cancer cell line harboring BRAF G469A in culture, and prevented Mekinist (trametinib)-related activation of AKT and resulted in increased induction of apoptosis compared to either agent alone (PMID: 25706985). | 25706985 |
| BRAF G469A | lung adenocarcinoma | sensitive | PLX8394 | Preclinical - Cell line xenograft | Actionable | In a preclinical study, PLX8394 decreased growth of lung adenocarcinoma cell lines harboring BRAF G469A in culture, and reduced tumor growth in xenograft models (PMID: 27834212). | 27834212 | |
| BRAF G469A | head and neck cancer | sensitive | Ulixertinib | Case Reports/Case Series | Actionable | In a Phase I trial, treatment with Ulixertinib (BVD-523) resulted in a partial response in two patients harboring BRAF G469A, including one patient with head and neck cancer and one patient with small bowel cancer (PMID: 29247021; NCT01781429). | 29247021 | |
| BRAF G469A | small intestine carcinoma | sensitive | Ulixertinib | Case Reports/Case Series | Actionable | In a Phase I trial, treatment with Ulixertinib (BVD-523) resulted in a partial response in two patients harboring BRAF G469A, including one patient with head and neck cancer and one patient with small bowel cancer (PMID: 29247021; NCT01781429). | 29247021 | |
| BRAF G469A | lung non-small cell carcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Encorafenib + Trametinib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of Braftovi (encorafenib) to treatment with Mekinist (trametinib) resulted in increased growth inhibition in a non-small cell lung cancer cell line harboring BRAF G469A in culture (PMID: 29903896). | 29903896 |
| BRAF G469A | lung non-small cell carcinoma | conflicting | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib + Vemurafenib | Preclinical - Cell culture | Actionable | In a preclinical study, the addition of Zelboraf (vemurafenib) to treatment with Mekinist (trametinib) resulted in increased proliferation compared to Mekinist (trametinib) alone in a non-small cell lung cancer cell line harboring BRAF G469A in culture (PMID: 29903896). | 29903896 |
| BRAF G469A | lung non-small cell carcinoma | sensitive | Dabrafenib | Preclinical - Cell culture | Actionable | In a preclinical study, Tafinlar (dabrafenib) treatment did not result in significant growth inhibition in a non-small lung cancer cell line harboring BRAF G469A in culture (PMID: 29903896). | 29903896 | |
| BRAF G469A | lung cancer | resistant | RMC-4550 | Preclinical - Cell culture | Actionable | In a preclinical study, RMC-4550 did not inhibit Erk phosphorylation or proliferation of lung cancer cells harboring BRAF G469A in culture (PMID: 30104724). | 30104724 | |
| BRAF G469A | Advanced Solid Tumor | resistant | Vemurafenib | Clinical Study - Cohort | Actionable | In a Phase II trial (MyPathway), Zelboraf (vemurafenib) treatment resulted in an objective response in only 4% (1/23) of patient with advanced solid tumors harboring non-V600 BRAF mutations, 2 of the non-responding patients harbored BRAF G469A (PMID: 29320312; NCT02091141). | 29320312 | |
| BRAF G469A | lung non-small cell carcinoma | resistant | Vemurafenib | Case Reports/Case Series | Actionable | In a Phase II trial, Zelboraf (vemurafenib) treatment did not result in response in the cohort of 15 non-small cell lung cancer patients with non-V600 BRAF mutations, which included 3 patients harboring BRAF G469A, and enrollment in this cohort was discontinued (PMID: 31959346; NCT02304809). | 31959346 | |
| BRAF G469A | lung adenocarcinoma | conflicting | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Case Reports/Case Series | Actionable | In a Phase II trial (NCI-MATCH), Mekinist (trametinib) treatment did not demonstrate clinical activity in patients with advanced solid tumors or lymphoma harboring BRAF fusion or non-V600 mutations, resulted in stable disease in a patient with lung adenocarcinoma harboring BRAF G469A, who remained on therapy for 20.4 months without progression (PMID: 31924734; NCT02465060). | 31924734 |
| BRAF G469A | melanoma | sensitive | PLX8394 | Preclinical - Cell culture | Actionable | In a preclinical study, PLX8394 treatment inhibited Erk signaling and reduced proliferation of melanoma cells harboring BRAF G469A in culture (PMID: 30559419). | 30559419 | |
| BRAF G469A | lung adenocarcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF G469A were sensitive to the combination treatment of Tafinlar (dabrafenib) and Mekinist (trametinib) in culture, demonstrating inhibition of cell growth (PMID: 32540409). | 32540409 |
| BRAF G469A | lung adenocarcinoma | conflicting | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF G469A were sensitive to treatment with Mekinist (trametinib) in culture, demonstrating inhibition of cell growth (PMID: 32540409). | 32540409 |
| BRAF G469A | lung adenocarcinoma | sensitive | Lifirafenib | Preclinical - Patient cell culture | Actionable | In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF G469A were sensitive to treatment with Lifirafenib (BGB-283) in culture, demonstrating inhibition of cell growth (PMID: 32540409). | 32540409 | |
| BRAF G469A | lung adenocarcinoma | sensitive | LXH 254 | Preclinical - Patient cell culture | Actionable | In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF G469A were sensitive to treatment with LXH 254 in culture, demonstrating inhibition of cell growth (PMID: 32540409). | 32540409 | |
| BRAF G469A | lung adenocarcinoma | resistant | Dabrafenib | Preclinical - Patient cell culture | Actionable | In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF G469A were resistant to treatment with Tafinlar (dabrafenib) in culture (PMID: 32540409). | 32540409 | |
| BRAF G469A | lung adenocarcinoma | resistant | Vemurafenib | Preclinical - Patient cell culture | Actionable | In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF G469A were resistant to treatment with Zelboraf (vemurafenib) in culture (PMID: 32540409). | 32540409 | |
| BRAF G469A | lung adenocarcinoma | resistant | Tovorafenib | Preclinical - Patient cell culture | Actionable | In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF G469A were resistant to treatment with Ojemda (tovorafenib) in culture (PMID: 32540409). | 32540409 | |
| BRAF G469A | lung adenocarcinoma | resistant | Ulixertinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF G469A were resistant to treatment with Ulixertinib (BVD-523) in culture (PMID: 32540409). | 32540409 | |
| BRAF G469A | lung adenocarcinoma | resistant | Ravoxertinib | Preclinical - Patient cell culture | Actionable | In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF G469A were resistant to treatment with Ravoxertinib (GDC-0994) in culture (PMID: 32540409). | 32540409 | |
| BRAF G469A | lung adenocarcinoma | resistant | MK-8353 | Preclinical - Patient cell culture | Actionable | In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF G469A were resistant to treatment with MK-8353 in culture (PMID: 32540409). | 32540409 | |
| BRAF G469A | lung adenocarcinoma | resistant | LY3214996 | Preclinical - Patient cell culture | Actionable | In a preclinical study, cells derived from a lung adenocarcinoma patient harboring BRAF G469A were resistant to treatment with LY3214996 in culture (PMID: 32540409). | 32540409 | |
| BRAF G469A | lung non-small cell carcinoma | sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Dabrafenib + Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, treatment with the combination of Mekinist (trametinib) and Tafinlar (dabrafenib) resulted in a reduction of the liver tumor and stable disease in the brain lesion in a patient with non-small cell lung cancer harboring BRAF G469A (PMID: 32981611). | 32981611 |
| BRAF G469A | colorectal cancer | not predictive | Cetuximab | Case Reports/Case Series | Actionable | In a clinical study, Erbitux (cetuximab) treatment as a third-line therapy resulted in stable disease with progression-free survival of 2.8 months in a patient with metastatic colorectal cancer harboring BRAF G469A (PMID: 31515458). | 31515458 | |
| BRAF G469A | colorectal cancer | not predictive | Cetuximab + Fluorouracil + Irinotecan + Leucovorin | Case Reports/Case Series | Actionable | In a clinical study, the combination of Erbitux (cetuximab) with FOLFIRI as a third-line therapy resulted in stable disease with a PFS of 4.4 months in a patient with metastatic colorectal cancer harboring BRAF G469A (PMID: 31515458). | 31515458 | |
| BRAF G469A | colorectal cancer | not predictive | Cetuximab + Irinotecan | Case Reports/Case Series | Actionable | In a clinical study, the combination of Erbitux (cetuximab) with Camptosar (irinotecan) as a third-line therapy resulted in stable disease with a PFS of 3.5 months in a patient with metastatic colorectal cancer harboring BRAF G469A (PMID: 31515458). | 31515458 | |
| BRAF G469A | colorectal cancer | not predictive | Irinotecan + Panitumumab | Case Reports/Case Series | Actionable | In a clinical study, the combination of Vectibix (panitumumab) with Camptosar (irinotecan) as a third-line therapy resulted in stable disease with a PFS of 4.0 months in a patient with metastatic colorectal cancer harboring BRAF G469A (PMID: 31515458). | 31515458 | |
| BRAF G469A | Advanced Solid Tumor | sensitive | IHMT-RAF-128 | Preclinical - Cell culture | Actionable | In a preclinical study, IHMT-RAF-128 inhibited proliferation of a cell line expressing BRAF G469A in culture (PMID: 37164118). | 37164118 | |
| BRAF G469A | lung non-small cell carcinoma | sensitive | SIJ777 | Preclinical - Cell culture | Actionable | In a preclinical study, SIJ777 inhibited proliferation of a non-small cell lung cancer cell line harboring BRAF G469A in culture (PMID: 33917428). | 33917428 | |
| BRAF G469A | lung non-small cell carcinoma | sensitive | PF-07799933 | Preclinical - Pdx | Actionable | In a preclinical study, PF-07799933 treatment resulted in tumor regression in a patient-derived xenograft (PDX) model of non-small cell lung cancer harboring BRAF G469A (PMID: 38691346). | 38691346 | |
| BRAF G469A | lung sarcomatoid carcinoma | sensitive | MEK inhibitor (Pan) | NST-628 | Preclinical - Pdx | Actionable | In a preclinical study, NST-628 treatment resulted in an overall response rate of 69.5% in a panel of patient-derived xenograft (PDX) models of solid tumors harboring RAS-MAPK pathway alterations, including a response in a lung sarcomatoid carcinoma patient-derived xenograft (PDX) model harboring BRAF G469A (PMID: 38588399). | 38588399 |
| BRAF G469A | invasive bladder transitional cell carcinoma | predicted - sensitive | MEK inhibitor (Pan) MEK1 Inhibitor MEK2 Inhibitor | Trametinib | Case Reports/Case Series | Actionable | In a clinical case study, Mekinist (trametinib) treatment resulted in a partial response and stable disease lasting more than 18 months in a patient with muscle-invasive urothelial bladder carcinoma harboring BRAF G469A (PMID: 39224677). | 39224677 |